Mass spectrometry is an analytical methodology used for qualitative and quantitative determination of chemical compounds in a chemical or biological sample. Analytes in a sample are ionized, separated according to their mass by a spectrometer and detected to produce a mass spectrum. The mass spectrum provides information about the masses and in some cases the quantities of the various analytes that make up the sample. In particular embodiments, mass spectrometry can be used to determine the molecular weight or the molecular structure of an analyte in a sample. Because mass spectrometry is fast, specific and sensitive, mass spectrometer devices have been widely used for the rapid identification and characterization of biological analytes.
Mass spectrometers may be configured in many different ways, but are generally distinguishable by the ionization methods employed and the ion separation methods employed. For example, in certain devices parent analyte ions are isolated, the parent ions are fragmented to produce daughter ions and the daughter ions are subjected to mass analysis. The identity and/or structure of the parent analyte ion can be deduced from the masses of the daughter ions. Such devices, generally referred to as tandem mass spectrometers (or MS/MS devices) may be coupled with a liquid chromatography system (e.g., an HPLC system or the like) and a suitable ion source (e.g. an electrospray ion source) to investigate analytes in a liquid sample.
In certain cases, a parent ion is first selected and then trapped in a collision cell. Fragmentation of the trapped parent ion is achieved by colliding the ion with neutral gas molecules or charged particles (e.g., other positively-charged or negatively-charged ions or electrons) to break covalent bonds within the ion. In these collisional methods, the energy produced by collision of a parent ion and a charged particle is redistributed within the parent ion, and the energy redistribution leads to dissociation (i.e., breakage) of covalent bonds within the parent ion. Covalent bonds having the lowest activation energy are usually broken to produce daughter ions. Such methodologies include collisional induced dissociation (CID) and electron capture dissociation (ECD), which are well known in the art.
Collision cells contain multipole devices and generally contain a plurality of elongated electrodes (e.g., conductive rods that may be hyperbolic or circular in cross-section) that lie parallel to each other and spaced from each other to form an ion passageway. A radio frequency (RF) voltage is applied to the electrodes to produce an oscillating electrical field which holds parent ions within the ion passageway, and charged particles or inert gas are introduced into the ion passageway to facilitate fragmentation of the parent ions. After a parent ion has been fragmented to produce daughter ions, the daughter ions are usually ejected into a mass spectrometer, typically a time of flight mass spectrometer (TOF-MS), a quadrupole mass analyzer or Fourier transform ion cyclotron resonance mass spectrometer (FTICR), for mass analysis. In certain cases, a particular daughter ion may be selected (i.e., filtered away from other daughter ions) in a mass filter, and combined with charged particles to further modify, e.g., fragment or alter the charge of, the daughter ion prior to mass analysis. Accordingly, reaction between ions and charged particles play an important role in many mass spectrometry methods.
Current methods for introducing charged particles into a collision cell involve introducing charged particles radially with respect to the ion passageway (e.g., through a space between two adjacent electrodes, or through a slot in an electrode; see, e.g., Schwartz et al (J. Am. Soc. Mass Spectrom. 2002 13:659-669) and Baba et al (Anal. Chem. 2004 76:4263-4266)). However, these methods for introducing charged particles into a collision cell are less than optimal because the charged particles are generally forced to pass through an RF field. The RF field represents a significant barrier for charged particles to cross, and, accordingly, the vast majority of charged particles are deflected prior to reaching the ion passageway in such methods. Further, passage of a charged particle through an RF field can lead to a significant change in the energy of the charged particle. As such, even if a charged particle makes it through the RF field to the ion passageway, it may have insufficient energy to initiate parent ion cleavage. Current methods for introducing charged particles into a collision cell are therefore inefficient. In certain prior art systems, a slot is constructed in an electrode. The slot causes an undesirable potential distortion within the oscillating multipole field. To achieve maximal performance of a multipole field, such distortion is undesirable.
Accordingly, there is still a great need for new methods for introducing charged particles into a collision cell. This invention meets this need, and others.